Research in recent years has shown that ultrasound can enhance clot lysis in the presence of thrombolytic agents such as t-PA or urokinase. The innovative aspect of this proposal is to explore these advances in an in vivo rabbit femoral artery model of the human middle cerebral artery to develop a noninvasive and cost effective method of thrombolysis monitoring and therapy in stroke. Advances in digital Doppler technology at Spencer Technologies enable a new dual approach to monitoring the degree of cerebral arterial recanalization while concurrently enhancing thrombolytic agent activity with ultrasound. Both of these activities-monitoring and therapy enhancement-can be done through the same transcranial ultrasound probe. The monitoring activity includes easy location of cerebral circulation using a digital Doppler color m-mode display, a format easily taught to medical professionals who are not Doppler ultrasound experts. Enhancing performance of thrombolytic agents with external ultrasound is anticipated to result in less thrombolytic agent required to accomplish restoration of blood flow to an infarcted region of the brain, and thereby decrease the incidence of hemorrhagic complication. This technology is important for reducing neurologic deficit associated with stroke and increasing the fraction of eligible patients who actually receive thrombolytic therapy. PROPOSED COMMERCIAL APPLICATIONS: This proposal comprises a platform for development of a Doppler ultrasound device which monitors cerebral blood flow velocity and concurrently enhances the thrombolytic effect of t-PA. The product produced will be specifically targeted at hospital emergency services. TCD is the only modality that exists for real time detection of cerebral blood flow during the early stages of stroke. No commercially available modality currently exists for enhancing thrombolytic therapy with ultrasound.